Patients with immunodeficiency are typically excluded from trials involving Immunotherapy, however they are at increased risk of developing malignancy. There is currently a lack of evidence to guide clinicians making difficult decisions in this cohort who have a theoretical risk of being unable to mount an adequate immune response.
Patients diagnosed with Metastatic Melanoma treated with either single or dual immunotherapy regimes at University Hospital Southampton NHS Foundation Trust were identified through our electronic chemotherapy prescribing system. Those with a background of immunosuppressive states were analysed including high intensity chemotherapy or stem cell transplant for prior malignancy and HIV.
A total of 124 patients received Pembrolizumab monotherapy and 47 patients received Iplimumab with Nivolumab. Six patients were considered immunodeficient, including three patients treated with curative intent with intensive chemotherapy for prior lymphoma, one patient with HIV with undetectable viral load, one patient continuing on Ibrutinib treatment for Small Lymphocytic Lymphoma and one patient under a watch and wait approach for Chronic Lymphocytic Leukaemia. All patients in this group had any grade treatment related toxicity, with five experiencing severe grade 3-4 toxicity requiring hospitalisation. With a median follow up of 16.5 months no patients had reactivation of previous malignancy. Four out of six patients have had a complete radiological response and two patients had disease progression.
In our cohort the majority of patients had a significant response to immunotherapy with toxicity managed without any long-term comorbidity. These patients were able to mount an anti-tumour immune response despite concurrent immunodeficiency and experienced an increased incidence of toxicity when compared with other patients treated at our centre. Despite the limitations of a small retrospective series our data would support offering immunotherapy even in the context of apparent immunodeficient states.
Clinical trial identification
Legal entity responsible for the study
University Hospitals Southampton.
Has not received any funding.
J. Longley: ESMO Travel Grant. I. Karydis: Travel, accommodations, expenses: Delcath Systems. M. Wheater: Consulting or advisory role: Roche, Novartis, MSD, Healthcare at Home; Travel, accommodations, expenses: MSD, Bayer, Bristol-Myers Squibb; Honoraria: Bristol-Myers Squibb, MSD Oncology, Pfizer, GlaxoSmithKline, Novartis, Delcath Systems; Research funding: Roche, GlaxoSmithKline, Novartis, MSD, Aveo, Bristol-Myers Squibb, Verastem, Merck Sharp & Dohme, Inovio Pharmaceuticals, BioNTech AG, Serametrix, Touchlight Genetics, Delcath Systems. C. Ottensmeier: Consulting or advisory role: Bristol-Myers Squibb, Merck Sharp & Dohme, Immatics; Travel, accommodations, expenses: Bristol-Myers Squibb, Merck Sharp & Dohme, Roche, Delcath Systems; Research funding: Bristol-Myers Squibb, Verastem, Merck Sharp & Dohme, Inovio Pharmaceuticals, BioNTech AG, Serametrix, Touchlight Genetics, Delcath Systems. All other authors have declared no conflicts of interest.